CAUSE AND EFFECTS

Irreversible phosphorylation of acetylcholinesterase

What mechanism causes the deadly and prolonged effects of organophosphates?

Inhibition of the desmolase enzyme

What mechanism, enacted by aminoglutethimide, blocks the conversion of cholesterol to pregnenolone?

Blockade of the conversion of progesterone into 11-Deoxycorticosterone

What specific effect results from a deficiency of 21 beta-Hydroxylase (P450c21), leading to salt wasting?

Reduced conversion of 11-Deoxycorticosterone into corticosterone

What specific effect results from a deficiency of 11 beta-Hydroxylase (P450c11), leading to salt wasting?

Reduced conversion of pregnenolone into 17-Hydroxy-pregnenolone

What specific effect results from a deficiency of 17 alpha-Hydroxylase (P450c17), which does not lead to salt-wasting symptoms?

Blockade of cholesterol side-chain cleavage and cytochrome P450 enzymes

What mechanism is enacted by Ketoconazole to decrease elevated glucocorticoid levels in Cushing’s syndrome?

Inhibition of steroid 11-hydroxylation

What specific mechanism is used by Metyrapone to selectively interfere with cortisol and corticosterone synthesis?

Activation of mineralocorticoid (aldosterone) receptors

What is the primary mechanism of action of fludrocortisone, leading to increased sodium reabsorption and hydrogen excretion?

Moderate activation of glucocorticoid receptors

What secondary mechanism of fludrocortisone leads to toxicities like muscle wasting, osteoporosis, glucose intolerance, and behavioral changes?

Increases sodium reabsorption and hydrogen excretion

What physiological effect occurs in the collecting tubules of the kidney when fludrocortisone acts as a strong agonist of mineralocorticoid receptors?

Salt and fluid retention

What toxicity of fludrocortisone can lead to hypertension and congestive heart failure?

Hypokalemia

What condition might occur in severe cases of fludrocortisone toxicity, especially when given with loop and thiazide diuretics?

Sustained therapy with moderate dosage accelerates recovery and decreases mortality

What effect do glucocorticoids have on Acute Respiratory Distress Syndrome?

Glucocorticoids suppress inflammation and immune response

What mechanism is utilized when glucocorticoids are prescribed for hematologic and inflammatory disorders?

Hastens fetal lung maturation

What therapeutic effect is achieved by administering glucocorticoids like Betamethasone before 34 weeks' gestation?

Gradually reducing the dose of an exogenous steroid medication

What process, known as slow dose-tapering, is necessary to allow the body's natural hormone production to resume after long-term steroid therapy?

Adrenal insufficiency (Adrenal crisis)

What severe condition would result if a patient is abruptly withdrawn from long-term exogenous steroid therapy?

Elevated glucocorticoid levels

What is the root cause of Cushing's Syndrome?

Increased appetite, obesity, and negative nitrogen balance

What set of metabolic effects are clinical features of Cushing's Syndrome?

Avascular necrosis of the femoral head and increased susceptibility to infection

What two severe effects are clinical manifestations of Cushing's Syndrome?

The most common cause is exogenous steroid intake

What is the etiology of Iatrogenic Cushing's Syndrome?

Directly inhibiting the Potassium-Hydrogen-ATPase pump

What mechanism makes Proton Pump Inhibitors (PPIs) the most effective class of acid controllers?

Making the pH of the stomach less acidic

What is the primary mechanism by which antacids relieve epigastric pain?

Coating ulcers or increasing mucus production in the stomach

What protective mechanism is utilized by Mucosal Resistance Enhancers like sucralfate and bismuth chelate?

Bacteria change and become resistant to the antibiotics

What causes antibiotic resistance?

Over-prescribing of antibiotics, lack of hygiene/sanitation, and patients not finishing their treatment

What three factors cause antibiotic/antimicrobial resistance?

Patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period of time and duration, and at the lowest cost

What does Rational Drug Use require according to the WHO (2016)?

Higher dose is required to produce a given response

What happens to a drug's effect when the body develops tolerance (desensitization)?

Altering societal structures and underlying determinants of health

What is the mechanism of Primordial Prevention?

Altering exposures that lead to disease

What is the mechanism of Primary Prevention?

Detect and treat pathological process at an earlier stage when treatment can be more effective

What is the mechanism of Secondary Prevention?

Prevents relapses and further deterioration via follow-up care and rehabilitation

What is the mechanism of Tertiary Prevention?

Increased Gram-negative activity

What happens to the spectrum of cephalosporins as the generation increases?

Increased Gram-positive activity

What happens to the spectrum of quinolones as the generation increases?

It is not appropriate to prescribe antitussives

What decision must be made if a patient's cough is productive (producing a lot of phlegm)?

Increases excretion of phlegm

What is the desired effect of prescribing mucolytics for a productive cough?

Risk of bleeding

What is the major complication when a patient is concurrently given two anticoagulants (e.g., enoxaparin and apixaban)?

The mechanism of action is the same

What is the problem when a patient is given enalapril and losartan together?

Pharmacists or nurses may mistake one drug for another

What is the primary cause of Care Management Problems?

Increased potassium chloride (KCl) administration

What can happen if a nurse misreads "9 doses" as "9 days" for a KCl prescription?

The dose or plasma concentration rises above the therapeutic range

What is the cause of a Toxic Effect of a drug?

An appreciably harmful or unpleasant reaction, which predicts hazard from future administration

What warrants prevention or specific treatment, or alteration of the dosage regimen, or withdrawal of the product, according to the definition of Adverse Drug Reaction (ADR)?

The use of medications can result in potential harms

What is the binding concept that connects ADRs and medication errors?

Drug prescribing by physicians

What is the most common source of prescription error (39%)?

Dose-related pharmacological response traceable to pharmacodynamics

What is the etiology of a Type A (Augmented) Adverse Drug Reaction?

Non-pharmacological response, often an allergic or idiosyncratic reaction

What is the etiology of a Type B (Bizarre) Adverse Drug Reaction?

Long-term effects coming from prolonged medication use

What is the etiology of a Type C (Continuous) Adverse Drug Reaction, such as osteoporosis from oral steroids?

A lag time where prolonged use leads to a delayed effect (e.g., teratogenic effects)

What is the etiology of a Type D (Delayed) Adverse Drug Reaction?

Withdrawal-type reactions when the drug intake is stopped

What is the etiology of a Type E (End-of-use) Adverse Drug Reaction, such as increased anxiety upon benzodiazepine cessation?

Failure of response (e.g., failure of antimicrobials due to the development of resistance)

What is the etiology of a Type F (Failure) Adverse Drug Reaction?

The dose that produces toxicity (TD50) to the dose needed for therapeutic response (ED50)

What defines the Therapeutic Index (TI)?

It takes a larger concentration from the effective dose to produce a toxic effect

What does a Higher Therapeutic Index indicate?

An addition of a smaller dose can result in a toxic effect

What does a Lower Therapeutic Index indicate?

Anaphylactoid reaction and shunting to the leukotriene pathway

What is the probable mechanism leading to severe bronchospasm and coma in a patient with Ibuprofen allergy (Type B ADR)?

Increased CNS excitation, memory, locomotor activity, and gastric acid secretion

What effects result from the activation of M1 muscarinic receptors?

Decrease in heart rate, force, and AV conduction

What effects result from the activation of M2 (Cardiac M2) muscarinic receptors in the heart?

Smooth muscle contraction, glandular secretion, and vasodilation (via EDRF/NO release)

What effects result from the activation of M3 muscarinic receptors?

Increase IP3 and DAG, resulting in increased calcium concentration

What secondary messenger effect occurs when M1, M3, and M5 receptors are activated (Gq-coupled)?

Inhibition of adenylyl cyclase (decreasing cAMP) and opening of potassium channels

What secondary messenger effect occurs when M2 and M4 receptors are activated (Gi/o-linked)?

Depolarization of the nerve cell or neuromuscular end plate membrane

What event occurs when an agonist binds to nicotinic receptors, opening channels for Na+, K+, and sometimes Ca2+?

Contraction (miosis) and contraction for near vision (accommodation)

What effect results from the activation of muscarinic receptors (M3) in the eye (iris sphincter and ciliary muscles)?

Decrease heart rate (negative chronotropy), decrease contractile strength (atria), and decrease conduction velocity (AV node)

What cardiac effects result from muscarinic receptor activation (M2)?

Dilation (via EDRF/NO)

What effect results from the activation of muscarinic receptors (M3/M5) on blood vessels?

Contraction (bronchoconstriction) and glandular secretion

What pulmonary effects result from muscarinic receptor activation (M3)?

Increase in motility, relaxation of sphincters, and secretion stimulation

What GI effects result from muscarinic receptor activation (M3)?

Contraction of the detrusor muscle and relaxation of the trigone/sphincter

What urinary effects result from muscarinic receptor activation (M3), leading to micturition?

Blocks acetylcholinesterase, making acetylcholine more available for binding

What is the mechanism of action of indirect-acting cholinomimetics (cholinesterase inhibitors)?

Forms free choline and acetylated enzyme

What is the product of the first step when acetylcholine binds to the active site of acetylcholinesterase and is hydrolyzed?

The formation of acetyl-enzyme is split via hydrolysis, yielding acetate

What is the outcome of the second step in the termination of action of acetylcholine?

Phosphorylation of the active site, forming an extremely stable bond

What mechanism causes the irreversible effects of organophosphates, which hydrolyze at a very slow rate?

Strengthened phosphorous-enzyme bond that cannot be broken anymore

What is the effect of the "aging" process in organophosphate poisoning?

The cholinergic syndrome is countered by producing sympathomimetic effects

What mechanism allows Atropine to be an effective antidote for organophosphate poisoning?

Bradycardia and decreased atrial/ventricular contractility

What cardiac effects are produced by moderate doses of cholinesterase inhibitors (indirect cholinergics) due to the predominance of the parasympathetic limb?

Increase strength of contraction

What therapeutic effect do low (therapeutic) doses of cholinesterase inhibitors have on muscles weakened by myasthenia gravis?

Fibrillations of the muscle fibers and fasciculations

What effect do higher doses of cholinesterase inhibitors have on skeletal muscles due to excessive acetylcholine (ACh)?

Autoimmune disease that attacks and destroys the neuromuscular junction (NMJ)

What is the underlying cause of Myasthenia Gravis?

Immunoglobulins cross-link with nicotinic receptors, stimulating internalization and degradation

What is the molecular mechanism of Myasthenia Gravis?

Increase availability of ACh at the motor end plate

What indirect effect of carbamates (Neostigmine and Pyridostigmine) causes the reversal of neuromuscular blockade?

The drug binds to free plasma rocuronium (or vecuronium), decreasing its plasma concentration

What is the first step in the mechanism of action of Sugammadex to reverse steroid NMBs?

A concentration gradient is created, causing rocuronium/vecuronium to transfer from the muscle to the plasma

What physiological response is generated by Sugammadex binding to the free NMB drug in the plasma?

Blocks the uptake of choline and slows ACh synthesis

What is the mechanism of action of Hemicholinium, an inhibitor of cholinergic transmission?

Prevents the storage and depletes acetylcholine in cholinergic terminals

What is the mechanism of action of Vesamicol, an inhibitor of cholinergic transmission?

Cleaves SNARE proteins (VAMPS/SNAPS), preventing ACh release

What mechanism makes Botulinum Toxin an inhibitor of acetylcholine release, causing paralysis?

Vasoconstriction and increased cytoplasmic Ca2+

What effect results from the activation of the Alpha 1 adrenergic receptor (Gq-coupled)?

Decreased adenylyl cyclase and cAMP (sympathetic inhibition)

What effect results from the activation of the Alpha 2 adrenergic receptor (Gi-coupled)?

Increased adenylyl cyclase and cAMP

What effect results from the activation of Beta adrenergic receptors (Gs-coupled)?

Cardiac stimulation (increased contractility and heart rate) and renin release

What effects result from the activation of the Beta 1 adrenergic receptor?

Bronchodilation, uterine relaxation, and relaxation of skeletal muscle vessels

What effects result from the activation of the Beta 2 adrenergic receptor?

Vasoconstriction, cardiac stimulation, and bronchodilation

What three primary effects result from Epinephrine activation (equal affinity for all receptors)?

Vasoconstriction, followed by increased mean arterial pressure

What primary effect of Norepinephrine causes the heart rate to decrease via the baroreceptor reflex?

Decreased sympathetic outflow when the drug reaches the CNS

What mechanism causes hypotension when centrally-acting Alpha 2 agonists like Clonidine or Methyldopa are administered?

Vasoconstriction, constriction of arterioles, and reduced blood flow to the nasal mucosa

What effects of Phenylephrine (Alpha 1 agonist) make it a popular decongestant?

Peripheral vasodilation

What is the primary effect of Fenoldopam (D1 agonist)?

Increases dopamine and norepinephrine levels in the prefrontal cortex

What mechanism is hypothesized for Methylphenidate when treating ADHD?

Inhibition of NET and promotion of NE release from presynaptic terminals

What two mechanisms allow Amphetamine and Methamphetamine to act as CNS stimulants and anorexiants?

Blocking NET, preventing the reuptake of norepinephrine

What mechanism causes Cocaine to increase sympathetic nervous activity (e.g., increased blood pressure, heart attack risk)?

Reuptakes most released norepinephrine back into the presynaptic neuron

What is the primary function of the Norepinephrine Transporter (NET) in terminating synaptic activity?

The tissue becomes less responsive to further stimulation

What happens to a cell or tissue after it has been exposed to an agonist for a period of time (desensitization)?

Require higher doses to produce a given response

What is the consequence of developing Tolerance (gradual desensitization)?

Loss of therapeutic efficiency

What effect occurs in Refractoriness (a form of tolerance)?